TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4806	14641;14642;14643	chr2:178736030;178736029;178736028	chr2:179600757;179600756;179600755
N2AB	4489	13690;13691;13692	chr2:178736030;178736029;178736028	chr2:179600757;179600756;179600755
N2A	3562	10909;10910;10911	chr2:178736030;178736029;178736028	chr2:179600757;179600756;179600755
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-31
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1586
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/A	rs2081384233	None	0.454	N	0.387	0.234	0.242244723065	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
T/A	rs2081384233	None	0.454	N	0.387	0.234	0.242244723065	gnomAD-4.0.0	6.57479E-06	None	None	None	None	N	None	0	6.55222E-05	None	0	0	None	0	0	0	0	0
T/I	None	None	0.669	N	0.513	0.218	0.437100570223	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.0769	likely_benign	0.075	benign	-0.794	Destabilizing	0.454	N	0.387	neutral	N	0.429303769	None	None	N
T/C	0.4203	ambiguous	0.4172	ambiguous	-0.316	Destabilizing	0.998	D	0.533	neutral	None	None	None	None	N
T/D	0.6536	likely_pathogenic	0.7641	pathogenic	-0.505	Destabilizing	0.842	D	0.556	neutral	None	None	None	None	N
T/E	0.5721	likely_pathogenic	0.703	pathogenic	-0.303	Destabilizing	0.842	D	0.561	neutral	None	None	None	None	N
T/F	0.4606	ambiguous	0.5645	pathogenic	-0.51	Destabilizing	0.949	D	0.584	neutral	None	None	None	None	N
T/G	0.3082	likely_benign	0.325	benign	-1.209	Destabilizing	0.728	D	0.519	neutral	None	None	None	None	N
T/H	0.4921	ambiguous	0.5835	pathogenic	-1.173	Destabilizing	0.998	D	0.521	neutral	None	None	None	None	N
T/I	0.2551	likely_benign	0.2962	benign	0.29	Stabilizing	0.669	D	0.513	neutral	N	0.391881639	None	None	N
T/K	0.4879	ambiguous	0.6548	pathogenic	0.064	Stabilizing	0.842	D	0.558	neutral	None	None	None	None	N
T/L	0.1429	likely_benign	0.1652	benign	0.29	Stabilizing	0.007	N	0.258	neutral	None	None	None	None	N
T/M	0.1231	likely_benign	0.1424	benign	0.123	Stabilizing	0.949	D	0.571	neutral	None	None	None	None	N
T/N	0.2508	likely_benign	0.3021	benign	-0.589	Destabilizing	0.801	D	0.511	neutral	N	0.510874668	None	None	N
T/P	0.5573	ambiguous	0.7341	pathogenic	-0.04	Destabilizing	0.966	D	0.613	neutral	D	0.546132476	None	None	N
T/Q	0.4397	ambiguous	0.5489	ambiguous	-0.341	Destabilizing	0.974	D	0.603	neutral	None	None	None	None	N
T/R	0.3673	ambiguous	0.5333	ambiguous	-0.203	Destabilizing	0.949	D	0.613	neutral	None	None	None	None	N
T/S	0.1462	likely_benign	0.1439	benign	-0.922	Destabilizing	0.022	N	0.141	neutral	N	0.49524449	None	None	N
T/V	0.1667	likely_benign	0.1742	benign	-0.04	Destabilizing	0.525	D	0.407	neutral	None	None	None	None	N
T/W	0.8405	likely_pathogenic	0.9069	pathogenic	-0.628	Destabilizing	0.998	D	0.518	neutral	None	None	None	None	N
T/Y	0.4859	ambiguous	0.5917	pathogenic	-0.202	Destabilizing	0.991	D	0.575	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.